The molecular structure of the aggregates of purified sickle cell hemoglobin, and the pathways by which these aggregates are formed and broken down, will be studied using three techniques: 1) using the interaction between sickle cell hemoglobin and other hemoglobins to define those regions of the hemoglobin surface which are involved in inter-molecular contacts in the aggregates, and those which are not; 2) following the kinetics of polymerization and de-polymerization after temperature jumps, by turbidimetry; and 3) preparing spin labels which will differ in their extent of binding to molecules free in solution, and molecules constrained in the aggregates, and hence which will provide an electron paramagnetic resonance probe of aggregation or gelation. The overall objective is to define in detail the molecular structure of the aggregates, and the molecular pathway of aggregation, to provide a rational basis for designing inhibitors of aggregation.